Pathogenic spirochetes bind and interact with various host structures and molecules throughout the course of infection. By utilizing their outer surface molecules, spirochetes can effectively modulate their dissemination, interact with immune system regulators, and select specific destination niches within the host. The three-dimensional structures of multiple spirochetal surface proteins have been elucidated, providing insight into their modus operandi. This review focuses on the structural characteristics of these sticky molecules and their functional implications, highlighting how these features contribute to the pathogenicity of spirochetes and their ability to persist in the host and vector environments. Recognizing the structural motifs and ligands to which these important virulence determinants bind could open new avenues for developing strategies to block colonization by spirochetal pathogens.

• Klíčová slova
• Borrelia, Leptospira, Treponema, adhesins, atomic structure, infection, lipoproteins, nuclear magnetic resonance, spirochetes, x‐ray crystallography,
• MeSH
• bakteriální proteiny chemie   MeSH
• interakce mikroorganismu a hostitele * MeSH
• lidé MeSH
• ligandy MeSH
• membránové proteiny chemie   MeSH
• Spirochaetales * chemie   MeSH
• spirochetové infekce * mikrobiologie   MeSH
• terciární struktura proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• bakteriální proteiny MeSH
• ligandy MeSH
• membránové proteiny MeSH

Lyme disease, a tick-borne illness caused by Borrelia spirochetes, poses a significant threat to public health. While acaricides effectively control ticks on pets and livestock, their impact on pathogen transmission is often unclear. This study investigated the acaricidal efficacy of fipronil against Ixodes ricinus ticks and its potential to block Borrelia afzelii transmission. Initially, we employed the ex vivo membrane blood-feeding system to assess the dose–response acaricidal activity of ivermectin, fipronil and its metabolite fipronil sulfone, when supplemented in the blood meal throughout tick feeding. To obtain the temporal resolution of their acaricidal activity, ticks were allowed to initiate blood feeding on an artificial membrane before being exposed to a 1-time topical application of these acaricides. Fipronil demonstrated superior speed of acaricidal activity, with onset of tick moribundity within a few hours, prompting its selection for further in vivo testing with Borrelia-infected ticks. The I. ricinus nymphs infected with B. afzelii were topically treated with fipronil shortly after attachment to mice. Four weeks post-feeding, the skin and internal organs were examined for the presence of Borrelia. No spirochetes were detected in any organ of mice exposed to fipronil-treated ticks, while 9 out of 10 control mice, exposed to non-treated infectious ticks, displayed Borrelia infection. The in vitro co-culture experiments confirmed that fipronil had no direct effect on Borrelia viability, indicating a tick-directed effect. Overall, these results underline the potential of fipronil as a valuable tool for tick control strategies and suggest a concept for acaricide-mediated Borrelia-transmission blockers.

• Klíčová slova
• Borrelia afzelii, Ixodes ricinus, Lyme disease, acaricide, ex vivo membrane blood feeding, fipronil, ivermectin, spirochetes, ticks,
• MeSH
• akaricidy * farmakologie   MeSH
• Borrelia burgdorferi komplex * účinky léků   fyziologie   MeSH
• klíště * mikrobiologie   účinky léků   MeSH
• lymeská nemoc * přenos   prevence a kontrola   mikrobiologie   MeSH
• myši MeSH
• nymfa mikrobiologie   účinky léků   MeSH
• pyrazoly * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akaricidy * MeSH
• fipronil MeSH Prohlížeč
• pyrazoly * MeSH

Infection with Borrelia burgdorferi often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical conditions of Lyme disease. While our apprehension of the spatial and temporal integration of the virulence determinants during the enzootic cycle of B. burgdorferi is constantly being improved, there is still much to be discovered. Many of the novel virulence strategies discussed in this review are undetermined. Lyme disease spirochaetes must surmount numerous molecular and mechanical obstacles in order to establish a disseminated infection in a vertebrate host. These barriers include borrelial relocation from the midgut of the feeding tick to its body cavity and further to the salivary glands, deposition to the skin, haematogenous dissemination, extravasation from blood circulation system, evasion of the host immune responses, localization to protective niches, and establishment of local as well as distal infection in multiple tissues and organs. Here, the various well-defined but also possible novel strategies and virulence mechanisms used by B. burgdorferi to evade obstacles laid out by the tick vector and usually the mammalian host during colonization and infection are reviewed.

• Klíčová slova
• Borrelia burgdorferi, Lyme disease, clinical manifestations, pathogenicity, tick-borne disease, virulence determinants,
• MeSH
• Borrelia burgdorferi * genetika   MeSH
• faktory virulence MeSH
• lidé MeSH
• lymeská nemoc * MeSH
• savci MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• faktory virulence MeSH

It has been demonstrated that impairing protein synthesis using drugs targeted against tRNA amino acid synthetases presents a promising strategy for the treatment of a wide variety of parasitic diseases, including malaria and toxoplasmosis. This is the first study evaluating tRNA synthetases as potential drug targets in ticks. RNAi knock-down of all tested tRNA synthetases had a strong deleterious phenotype on Ixodes ricinus feeding. Our data indicate that tRNA synthetases represent attractive, anti-tick targets warranting the design of selective inhibitors. Further, we tested whether these severely impaired ticks were capable of transmitting Borrelia afzelii spirochaetes. Interestingly, biologically handicapped I. ricinus nymphs transmitted B. afzelii in a manner quantitatively sufficient to develop a systemic infection in mice. These data suggest that initial blood-feeding, despite the incapability of ticks to fully feed and salivate, is sufficient for activating B. afzelii from a dormant to an infectious mode, enabling transmission and dissemination in host tissues.

• Klíčová slova
• Borrelia, Lyme disease, borreliosis, tRNA synthetase, tick, transmission,
• MeSH
• akaricidy farmakologie   MeSH
• aminoacyl-tRNA-synthetasy antagonisté a inhibitory   genetika   MeSH
• Borrelia burgdorferi komplex MeSH
• klíšťata účinky léků   mikrobiologie   MeSH
• lidé MeSH
• lymeská nemoc farmakoterapie   mikrobiologie   přenos   MeSH
• proteosyntéza účinky léků   MeSH
• vyvíjení léků MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akaricidy MeSH
• aminoacyl-tRNA-synthetasy MeSH

Lyme borreliosis is an emerging tick-borne disease caused by spirochetes Borrelia burgdorferi sensu lato. In Europe, Lyme borreliosis is predominantly caused by Borrelia afzelii and transmitted by Ixodes ricinus. Although Borrelia behavior throughout tick development is quite well documented, specific molecular interactions between Borrelia and the tick have not been satisfactorily examined. Here, we present the first transcriptomic study focused on the expression of tick midgut genes regulated by Borrelia. By using massive analysis of cDNA ends (MACE), we searched for tick transcripts expressed differentially in the midgut of unfed, 24h-fed, and fully fed I. ricinus nymphs infected with B. afzelii. In total, we identified 553 upregulated and 530 downregulated tick genes and demonstrated that B. afzelii interacts intensively with the tick. Technical and biological validations confirmed the accuracy of the transcriptome. The expression of five validated tick genes was silenced by RNA interference. Silencing of the uncharacterized protein (GXP_Contig_30818) delayed the infection progress and decreased infection prevalence in the target mice tissues. Silencing of other genes did not significantly affect tick feeding nor the transmission of B. afzelii, suggesting a possible role of these genes rather in Borrelia acquisition or persistence in ticks. Identification of genes and proteins exploited by Borrelia during transmission and establishment in a tick could help the development of novel preventive strategies for Lyme borreliosis.

• Klíčová slova
• Borrelia afzelii, Ixodes ricinus, RNAi, massive analysis of cDNA ends (MACE), midgut, tick, transcriptome,
• MeSH
• Borrelia burgdorferi komplex genetika   MeSH
• klíšťata genetika   mikrobiologie   MeSH
• klíště genetika   MeSH
• lymeská nemoc mikrobiologie   přenos   MeSH
• myši inbrední C3H MeSH
• myši MeSH
• nymfa mikrobiologie   MeSH
• transkriptom genetika   MeSH
• trávicí systém mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH